Progress and prospects: techniques for site-directed mutagenesis in animal models.

In the past 2 years, new gene-targeting approaches using adeno-associated virus and designer zinc-finger nucleases have been successfully applied to the production of genetically modified ferrets, pigs, mice and zebrafish. Gene targeting using these tools has been combined with somatic cell nuclear transfer and germ cell transplantation to generate gene-targeted animal models. These new technical advances, which do not require the generation of embryonic stem cell-derived chimeras, will greatly accelerate the production of non-mouse animal models for biomedical research.